Titanium-catalyzed highly stereoselective anti-Markovnikov intermolecular hydroalkoxylation of alkynes to prepare -enol ethers.

Enol ethers are essential synthetic frameworks and widely applied in organic synthesis; however, high regio- and stereo-selective access to enol ethers remains challenging. Herein, we report a titanium-catalyzed stereospecific anti-Markovnikov hydroalkoxylation reaction of alkynes for the synthesis of -enol ethers with excellent functional group tolerance and yields. Mechanistic studies showed that the titanium coordinates with the alkyne and then an oxygen anion attacks the π-bond of the alkyne from the backside to provide a -oxygen metallation intermediate, which accounts for the high -stereoselectivity. Furthermore, -enol ethers could be applied as a kind of synthon for late-stage transformations and gram-scale synthesis, which demonstrates their potential value in organic synthesis.